tbuckley/cabot-search huggingface dataset:
Younger haploidentical donor versus older matched unrelated donor for patients with <scp>AML</scp>/<scp>MDS</scp>
Authors: Curtis Marcoux, David Marin, Jeremy Ramdial, Gheath AlAtrash, Amin M. Alousi, Betul Oran, Partow Kebriaei, Uday R. Popat, Katayoun Rezvani, Richard E. Champlin, Elizabeth J. Shpall, Rohtesh S. Mehta
Journal: American Journal of Hematology (2023)

Optimal donor selection is fundamental to successful allogeneic hematopoietic cell transplantation (HCT), and donor age influences survival after both matched unrelated donor (MUD) and haploidentical donor HCT. Though recent studies have shown similar outcomes between MUD and haploidentical HCT, it is unknown if outcomes differ following HCT with younger haploidentical donors compared to HCT with older MUDs. Therefore, we performed a retrospective analysis comparing outcomes of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) patients who underwent HCT with younger (≤35 years) haploidentical donors (n = 494) or older (>35 years) MUDs (n = 1005). Patients in the haploidentical and MUD groups received post-transplant cyclophosphamide (PTCy) and conventional graft-versus-host-disease (GVHD) prophylaxis, respectively. In multivariate analysis, use of younger haploidentical donors was associated with improved overall survival (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.69-0.95, p = .01) and lower rates of grade II-IV acute GVHD (HR 0.64, 95% CI 0.53-0.77, p < .001), grade III-IV acute GVHD (HR 0.37, 95% CI 0.25-0.53, p < .001), and chronic GVHD (HR 0.49, 95% CI 0.40-0.60, p < .001). Relapse rates were similar among those who received myeloablative conditioning but were higher in patients of the younger haploidentical group who received reduced intensity conditioning (HR 1.49, 95%CI 1.18-1.88, p = .001). The younger haploidentical group had significantly lower non-relapse mortality ≥3 months post-HCT (HR 0.59, 95% CI 0.38-0.90, p = .02). Our data support the use of younger haploidentical donors with PTCy over older MUDs with conventional prophylaxis in patients with MDS or AML. Further studies on the importance of donor age in haploidentical and MUD HCT with PTCy prophylaxis are warranted.
18F-FMISO PET of an Intracranial Tuberculoma
Authors: Akihiko Sakata, Yasutaka Fushimi, Yoshiki Arakawa, Yoichi Shimizu, Yuji Nakamoto
Journal: Clinical Nuclear Medicine (2022)

Solitary intracranial tuberculomas are rare and frequently misdiagnosed as brain tumors. We report a case of intracranial tuberculous granuloma mimicking a high-grade glioma with avid uptake on 18 F-fluoromisonidazole PET/CT. It has been believed that hypoxia exists within the tuberculosis granuloma, and that this hypoxic environment causes Mycobacterium tuberculosis to lie dormant and asymptomatic infection to occur. This hypoxic and necrotic condition inside tuberculous granuloma may lead to high accumulation of 18 F-fluoromisonidazole in this case.
[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant
Authors: Ramsha Iqbal, Maqsood Yaqub, Huseyyin O. Bektas, Daniela E. Oprea-Lager, Elisabeth G.E. de Vries, Andor W.J.M. Glaudemans, Philippe Aftimos, Géraldine Gebhart, Andrew P. Beelen, Robert C. Schuit, Albert D. Windhorst, Ronald Boellaard, C. Willemien Menke-van der Houven van Oordt
Journal: Clinical Cancer Research (2023)

Abstract Purpose: PET with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]-fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER-positive breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant. Experimental Design: In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative, and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was progression-free survival (PFS). Results: The HS and PFS in the entire group did not correlate (n = 16, Spearman's rho, P = 0.06), but patients with a low HS (&amp;lt; 25.0%, n = 4) had a PFS of &amp;gt; 5 months whereas patients with no [18F]FES uptake (HS 100.0%, n = 3) had a PFS of &amp;lt; 2 months. [18F]FES uptake was not affected by estrogen receptor 1 (ESR1) mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES-positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned ≤ 1–2 half-lives of rintodestrant whereas it restored in patients scanned ≥ 5 days after end of treatment. Conclusions: Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs. See related commentary by Linden and Mankoff, p. 2015
Analysis of Psychiatric Disorders by Age Among Children Following a Mass Terrorist Attack in Nice, France, on Bastille Day, 2016
Authors: Florence Askenazy, Nicolas Bodeau, Ophélie Nachon, Mélanie Gittard, Michèle Battista, Arnaud Fernandez, Morgane Gindt
Journal: JAMA Network Open (2023)

This cross-sectional study examines psychiatric disorders among children after a mass terrorist attack in Nice, France, in 2016.
Microbial changes from bariatric surgery alters glucose-dependent insulinotropic polypeptide and prevents fatty liver disease
Authors: Tien S. Dong, William Katzka, Julianne C. Yang, Candace Chang, Nerea Arias-Jayo, Venu Lagishetty, Anna Balioukova, Yijun Chen, Erik Dutson, Zhaoping Li, Emeran A. Mayer, Joseph R. Pisegna, Claudia Sanmiguel, Jonathan P. Jacobs
Journal: Gut Microbes (2023)

Bariatric surgery remains a potent therapy for nonalcoholic fatty liver disease (NAFLD), but its inherent risk and eligibility requirement limit its adoption. Therefore, understanding how bariatric surgery improves NAFLD is paramount to developing novel therapeutics. Here, we show that the microbiome changes induced by sleeve gastrectomy (SG) reduce glucose-dependent insulinotropic polypeptide (GIP) signaling and confer resistance against diet-induced obesity (DIO) and NAFLD. We examined a cohort of NALFD patients undergoing SG and evaluated their microbiome, serum metabolites, and GI hormones. We observed significant changes in Bacteroides, lipid-related metabolites, and reduction in GIP. To examine if the changes in the microbiome were causally related to NAFLD, we performed fecal microbial transplants in antibiotic-treated mice from patients before and after their surgery who had significant weight loss and improvement of their NAFLD. Mice transplanted with the microbiome of patients after bariatric surgery were more resistant to DIO and NAFLD development compared to mice transplanted with the microbiome of patients before surgery. This resistance to DIO and NAFLD was also associated with a reduction in GIP levels in mice with post-bariatric microbiome. We further show that the reduction in GIP was related to higher levels of Akkermansia and differing levels of indolepropionate, bacteria-derived tryptophan-related metabolite. Overall, this is one of the few studies showing that GIP signaling is altered by the gut microbiome, and it supports that the positive effect of bariatric surgery on NAFLD is in part due to microbiome changes.
Whole-brain radiotherapy associated with structural changes resembling aging as determined by anatomic surface-based deep learning
Authors: Nikhil Rammohan, Alexander Ho, Pierre Besson, Tim J Kruser, S Kathleen Bandt
Journal: Neuro-Oncology (2023)

Abstract Background Brain metastases are the most common intracranial tumors in adults and are associated with significant morbidity and mortality. Whole-brain radiotherapy (WBRT) is used frequently in patients for palliation, but can result in neurocognitive deficits. While dose-dependent injury to individual areas such as the hippocampus has been demonstrated, global structural shape changes after WBRT remain to be studied. Methods We studied healthy controls and patients with brain metastases and examined MRI brain anatomic surface data before and after WBRT. We implemented a validated graph convolutional neural network model to estimate patient’s “brain age”. We further developed a mixed-effects linear model to compare the estimated age of the whole brain and substructures before and after WBRT. Results 4220 subjects were analyzed (4148 healthy controls and 72 patients). The median radiation dose was 30 Gy (range 25–37.5 Gy). The whole brain and substructures underwent structural change resembling rapid aging in radiated patients compared to healthy controls; the whole brain “aged” 9.32 times faster, the cortex 8.05 times faster, the subcortical structures 12.57 times faster, and the hippocampus 10.14 times faster. In a subset analysis, the hippocampus “aged” 8.88 times faster in patients after conventional WBRT versus after hippocampal avoidance (HA)-WBRT. Conclusions Our findings suggest that WBRT causes the brain and its substructures to undergo structural changes at a pace up to 13x of the normal aging pace, where hippocampal avoidance offers focal structural protection. Correlating these structural imaging changes with neurocognitive outcomes following WBRT or HA-WBRT would benefit from future analysis.
Characterization of Cell-Free DNA Size Distribution in Osteosarcoma Patients
Authors: Sasimol Udomruk, Areerak Phanphaisarn, Thanat Kanthawang, Apiwat Sangphukieo, Songphon Sutthitthasakul, Siripong Tongjai, Pimpisa Teeyakasem, Patcharawadee Thongkumkoon, Santhasiri Orrapin, Sutpirat Moonmuang, Jeerawan Klangjorhor, Arnat Pasena, Pathacha Suksakit, Sivamoke Dissook, Pitithat Puranachot, Jongkolnee Settakorn, Tonapha Pusadee, Dumnoensun Pruksakorn, Parunya Chaiyawat
Journal: Clinical Cancer Research (2023)

Cell-free DNA (cfDNA) analysis is a powerful tool for noninvasively predicting patient outcomes. We analyzed the size distribution of cfDNA and assessed its prognostic and diagnostic values in an osteosarcoma cohort.The fragment size distribution and level of cfDNA were analyzed in 15 healthy donors and 50 patients with osteosarcoma using automated capillary electrophoresis. The prognostic performance of cfDNA size analysis was assessed using univariate and multivariable analyses. By performing whole-genome sequencing of matched cfDNA and osteosarcoma tissue samples, we investigated the correlation between the size and mutation profiles of cfDNA and the mutation concordance between cfDNA and paired tissue tumors.The size of cfDNA fragments in patients with osteosarcoma was significantly shorter than in healthy donors, with the integrative analysis of size distribution and level of cfDNA achieving a high specificity and sensitivity of 100%. The short cfDNA fragment (150-bp cut-off) was an independent prognostic predictor in this osteosarcoma cohort [HR, 9.03; 95% confidence interval (CI), 1.13-72.20; P = 0.038]. Shortened cfDNA fragments were found to be a major source of mutations. Enrichment of cfDNA fragments with less than or equal to 150 bp by in silico size selection remarkedly improved the detection of copy-number variation signals up to 2.3-fold when compared with total cfDNA, with a higher concordance rate with matched osteosarcoma tissue.This finding demonstrated the potential of cfDNA size profiling in the stratification of poor prognostic patients with osteosarcoma. The short fragments of cfDNA are a promising source for boosting the detection of significant mutations in osteosarcoma. See related commentary by Weiser et al., p. 2017.
Genomic reconstruction and directed interventions in a multidrug-resistant Shigellosis outbreak in Seattle, WA, USA: a genomic surveillance study
Authors: Giannoula S Tansarli, Dustin R Long, Adam Waalkes, Lori A Bourassa, Stephen J Libby, Kelsi Penewit, Jared Almazan, Jason Matsumoto, Chloe Bryson-Cahn, Krista Rietberg, BreeAnna M Dell, Noël V Hatley, Stephen J Salipante, Ferric C Fang
Journal: The Lancet Infectious Diseases (2023)
Cancer Cells Employ the Most Prolific RNA Editors: A Closer Look at the Single-Cell Level
Authors: Yikai Luo, Han Liang
Journal: Cancer Research (2023)

Abstract Adenosine-to-inosine (A-to-I) RNA editing is a major source of nucleotide diversification that has significant mechanistic implications in cancer progression and treatment response. However, its activity and prevalence have not yet been systematically determined at a single-cell resolution. Chan and colleagues revealed widespread A-to-I RNA editing events in single cancer cells through an in-depth analysis of a public lung adenocarcinoma single-cell transcriptome dataset. Edits significantly enriched in cancer cells compared to other cell types have the potential to inhibit innate immune response and to predict poor therapeutic response and prognosis in patients treated with targeted therapies. See related article by Chan et al., p. 374
Low Vision Rehabilitation Service Utilization Before and After Implementation of a Clinical Decision Support System in Ophthalmology
Authors: Xinxing Guo, Michael V. Boland, Bonnie K. Swenor, Judith E. Goldstein
Journal: JAMA Network Open (2023)

Importance Electronic clinical decision support systems apply clinical guidelines in real time and offer a new approach to improve referral and utilization of low vision rehabilitation (LVR) care. Objective To characterize patients and factors associated with LVR service utilization with and without the use of an electronic health record (EHR) clinical decision support system (CDSS) alert. Design, Setting, and Participants Quality improvement study using EHR data to compare patients who did and did not utilize LVR service after referral between November 6, 2017, and October 5, 2019, (primary) and to assess overall service utilization rate from September 1, 2016, to April 2, 2021, regardless of referral status (secondary). Participants in the primary analysis were patients at a large ophthalmology department in an academic medical center in the US who received an LVR referral recommendation from their ophthalmologist according to the CDSS alert. The secondary analysis included patients with best documented visual acuity (BDVA) worse than 20/40 before, during, and after the CDSS implementation. Data were analyzed from August 2021 to April 2022. Exposures Number and locations of referral recommendations for LVR service according to the CDSS alert in the primary analysis; active CDSS implementation in the secondary analysis. Main Outcomes and Measures LVR service utilization rate was defined as the number of patients who accessed service among those who were referred (primary) and among those with BDVA worse than 20/40 (secondary). EHR data on patient demographics (age, sex, race, ethnicity) and ophthalmology encounter characteristics (numbers of referral recommendations, encounter location, and BDVA) were extracted. Results Of the 429 patients (median [IQR] age, 71 [53 to 83] years; 233 female [54%]) who received a CDSS-based referral recommendation, 184 (42.9%) utilized LVR service. Compared with nonusers of LVR, users were more likely to have received at least 2 referral recommendations (12.5% vs 6.1%; χ 2 1 = 5.29; P = .02) and at an ophthalmology location with onsite LVR service (87.5% vs 78.0%; χ 2 1 = 6.50; P = .01). Onsite LVR service (odds ratio, 2.06; 95% CI, 1.18-3.61) persisted as the only statistically significant factor after adjusting for patient demographics and other referral characteristics. Among patients whose BDVA was worse than 20/40 before, during, and after the CDSS implementation regardless of referral status, the LVR service utilization rate was 6.1%, 13.8%, and 7.5%, respectively. Conclusions and Relevance In this quality improvement study, ophthalmologist referral recommendations and onsite LVR services at the location where patients receive other ophthalmic care were significantly associated with service utilization. Ophthalmology CDSSs are promising tools to apply clinical guidelines in real time to improve connection to care.
Single-Cell Transcriptomics Reveals Immune Reconstitution in Patients with R/R T-ALL/LBL Treated with Donor-Derived CD7 CAR-T Therapy
Authors: Wei Chen, Hui Shi, Zhuojun Liu, Fan Yang, Jia Liu, Leqiang Zhang, Yajin Wu, Yuanshi Xia, Yuxuan Ou, Ruiting Li, Ting Zhang, Jiecheng Zhang, Xiaoyan Ke, Kai Hu, Jian Yu
Journal: Clinical Cancer Research (2023)

Abstract Purpose: CD7 chimeric antigen receptor T (CAR-T) therapy has potent antitumor activity against relapsed/refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL), however, immune reconstitution after CAR-T remains largely unknown. Patients and Methods: An open-label phase I clinical trial (ChiCTR2200058969) was initiated to evaluate safety and efficacy of donor-derived CD7 CAR-T cells in 7 R/R T-ALL/LBL patients. CAR-T cells were detected by flow cytometry and PCR. Cytokine levels were quantified by cytometric bead arrays. Single-cell RNA sequencing (scRNA-seq) was adopted to profile immune reconstitution. Results: Optimal complete remission (CR) was 100% on day 28, and median followed-up time was 4 months. Leukopenia, thrombocytopenia, and neutropenia were observed in 6 patients, and infections occurred in 5 patients. Two patients died of serious infection and one died of a brain hemorrhage. CAR-T cells expanded efficiently in all patients. CD7+ T cells were eliminated in peripheral blood on day 11 after infusion, and CD7− T cells dramatically expanded in all patients. scRNA-seq suggested that immunologic activities of CD7− T cells were stronger than those of T cells before infusion due to higher expression levels of T-cell function-related pathways, and major characters of such CD7− T cells were activation of autoimmune-related pathways. Monocyte loss was found in 2 patients who died of serious infections, indicating the main cause of the infections after infusion. S100A8 and S100A9 were identified as potential relapse markers due to their notable upregulation in leukocyte lineage in relapsed patients versus non-relapse controls. Conclusions: Our data revealed cellular level dynamics of immune homeostasis of CD7 CAR-T therapy, which is valuable for optimizing the treatment of R/R T-ALL/LBL.
Pre-Pregnancy eGFR and the Risk of Adverse Maternal and Fetal Outcomes: A Population-Based Study
Authors: Jessica Tangren, Lavanya Bathini, Nivethika Jeyakumar, Stephanie N. Dixon, Joel Ray, Ron Wald, Ziv Harel, Ayub Akbari, Anna Mathew, Susan Huang, Amit X. Garg, Michelle A. Hladunewich
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Pregnancies in women with CKD carry greater risk than pregnancies in the general population. The small number of women in prior studies has limited estimates of this risk, especially among those with advanced CKD. We report the results of a population-based cohort study in Ontario, Canada, that assessed more than 500,000 pregnancies, including 600 with a baseline eGFR &lt; 60 ml/min per 1.73 m 2 . The investigation demonstrates increases in risk of different adverse maternal and fetal outcomes with lower eGFR and further risk elevation with baseline proteinuria. Background CKD is a risk factor for pregnancy complications, but estimates for adverse outcomes come largely from single-center studies with few women with moderate or advanced stage CKD. Methods To investigate the association between maternal baseline eGFR and risk of adverse pregnancy outcomes, we conducted a retrospective, population-based cohort study of women (not on dialysis or having had a kidney transplant) in Ontario, Canada, who delivered between 2007 and 2019. The study included 565,907 pregnancies among 462,053 women. Administrative health databases captured hospital births, outpatient laboratory testing, and pregnancy complications. We analyzed pregnancies with serum creatinine measured within 2 years of conception up to 30 days after conception and assessed the impact of urine protein where available. Results The risk of major maternal morbidity, preterm delivery, and low birthweight increased monotonically across declining eGFR categories, with risk increase most notable as eGFR dropped below 60 ml/min per 1.73 m 2 . A total of 56 (40%) of the 133 pregnancies with an eGFR &lt;45 ml/min per 1.73 m 2 resulted in delivery under 37 weeks, compared with 10% of pregnancies when eGFR exceeded 90 ml/min per 1.73 m 2 . Greater proteinuria significantly increased risk within each eGFR category. Maternal and neonatal deaths were rare regardless of baseline eGFR (&lt;0.3% of all pregnancies). Only 7% of women with an eGFR &lt;45 ml/min per 1.73 m 2 received dialysis during or immediately after pregnancy. Conclusions We observed higher rates of adverse pregnancy outcomes in women with low eGFR with concurrent proteinuria. These results can help inform health care policy, preconception counseling, and pregnancy follow-up in women with CKD.
Gut microbiota alteration after cholecystectomy contributes to post-cholecystectomy diarrhea via bile acids stimulating colonic serotonin
Authors: Yayun Xu, Jianfa Wang, Xubo Wu, Hui Jing, Shilong Zhang, Zhiqiu Hu, Longhua Rao, Qimeng Chang, Lishun Wang, Ziping Zhang
Journal: Gut Microbes (2023)

Post-cholecystectomy diarrhea (PCD) is highly prevalent among outpatients with cholecystectomy, and gut microbiota alteration is correlated with it. However, how and to what extent changed fecal bacteria contributes to diarrhea are still unrevealed. Humanized gut microbiome mice model by fecal microbiota transplantation was established to explore the diarrhea-inducible effects of gut microbiota. The role of microbial bile acids (BAs) metabolites was identified by UPLC/MS and the underlying mechanisms were investigated with selective inhibitors and antagonists as probes. These mice transplanted with fecal microbiome of PCD patients (PCD mice) exhibited significantly enhanced gastrointestinal motility and elevated fecal water content, compared with these mice with fecal microbiome of NonPCD patients and HC. In analyzing gut microbiota, tryptophan metabolism was enriched in PCD microbiome. In addition, overabundant serotonin in serum and colon, along with elevated biosynthesis gene and reduced reuptake gene, and highly expressed 5-HT receptors (5-HTRs) in colon of PCD mice were found, but not in small intestine. Notably, diarrheal phenotypes in PCD mice were depleted by tryptophan hydroxylase 1 inhibitor (LX1606) and 5-HTRs selective antagonists (alosetron and GR113808). Furthermore, increased microbial secondary BAs metabolites of DCA, HDCA and LCA were revealed in feces of PCD mice and they were found responsible for stimulating 5-HT level in vitro and in vivo. Intriguingly, blocking BAs-conjugated TGR5/TRPA1 signaling pathway could significantly alleviate PCD. In conclusion, altered gut microbiota after cholecystectomy contributes to PCD by promoting secondary BAs in colon, which stimulates colonic 5-HT and increases colon motility.
18F-FDG PET/CT Imaging Post Heart Transplantation Depicts High Accumulation at Sites of Previous Ventricular Assist Device Insertion
Authors: Yoshitaka Toyama, Masayuki Otani, Nobuhiro Yaoita, Kentaro Takanami, Kei Takase
Journal: Clinical Nuclear Medicine (2023)

A 37-year-old man with previous heart transplantation for dilated cardiomyopathy underwent screening for malignancy under posttransplantation immunosuppression. 18 F-FDG PET/CT revealed uptake in 2 peritoneal sites of the pericardium that corresponded to the insertion sites of a left ventricular assist device that was used before transplantation. Additional abnormal uptake in the right axillary artery, aortic arch, and left femoral artery corresponded to the insertion sites for arterial inflow during cardiopulmonary bypass. Knowledge that FDG accumulation may occur at the insertion sites of an extracorporeal-circulation device enables unnecessary tests to be avoided.